1. Technical Field
Embodiments of the present invention relate to methods for treating GLUT1 and related brain energy deficiencies comprising administering odd-carbon fatty acid sources, e.g., C5 or C7 fatty acid sources, and related compositions.
2. Description of the Related Art
GLUT1 deficiency is a rare progressive neurogenetic disorder characterized by encephalopathy with progressive intellectual disability, drug-resistant epilepsy, motor disorders, and acquired microcephaly.1-4 The clinical spectrum of GLUT1 deficiency syndrome includes developmental delay and movement disorders without epilepsy,4 as well as familial and sporadic paroxysmal exercise-induced dyskinesia with or without epilepsy.5 There are varying degrees of cognitive impairment with dysarthria, dysfluency, and expressive language deficits that are more severe than receptive language deficits. In most patients, the cerebrospinal fluid (CSF) to blood glucose ratio is below 0.50, and CSF lactate is low to normal.3 GLUT1 deficiency can be diagnosed by mutation analysis of the SLC2A1 gene, and deficient GLUT1 function confirmed by analysis of glucose uptake into erythrocytes.
Early diagnosis of GLUT1 deficiency is critical because it allows for treatment with a ketogenic diet, a severely restricted diet consisting of 70-90% fat and very low carbohydrate diet that mimics the metabolic state of fasting. Ketogenic diets generate ketone bodies as an alternative energy source for the brain and can thereby reduce the frequency of seizures and dystonic movements.6,7 Because ketone bodies are not affected by the GLUT1 defect (ketone bodies use another transporter to enter the central nervous system), they can supply an alternative source of fuel to the brain, effectively correcting the brain energy metabolism deficiency.7 However, ketogenic diets are difficult to comply with long-term because of certain adverse side effects the extreme dietary choices require. Side effects of ketogenic diets include constipation, low-grade acidosis, hypoglycemia, hyperlipidemia and hypercholesterolemia. Long-term ketogenic diets may cause retarded growth, bone fractures, and kidney stones.8 
Accordingly, there remains a need in the art for treating GLUT1 deficiencies and similar defects in brain energy metabolism.